Therapy of human tumors in NOD/SCID mice with patient-derived reactivated memory T cells from bone marrow

Nat Med. 2001 Apr;7(4):452-8. doi: 10.1038/86523.


In an analysis of 84 primary-operated breast cancer patients and 11 healthy donors, we found that the bone marrow of most patients contained memory T cells with specificity for tumor-associated antigens. Patients' bone marrow and peripheral blood contained CD8+ T cells that specifically bound HLA/peptide tetramers. In short-term culture with autologous dendritic cells pre-pulsed with tumor lysates, patients' memory T cells from bone marrow (but not peripheral blood) could be specifically reactivated to interferon-gamma-producing and cytotoxic effector cells. A single transfer of restimulated bone-marrow T cells into NOD/SCID mice caused regression of autologous tumor xenotransplants associated with infiltration by human T cells and tumor-cell apoptosis and necrosis. T cells from peripheral blood showed much lower anti-tumor reactivity. Our findings reveal an innate, specific recognition of breast cancer antigens and point to a possible novel cancer therapy using patients' bone-marrow-derived memory T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Neoplasm / chemistry
  • Apoptosis
  • Bone Marrow Transplantation
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Female
  • HLA-A2 Antigen / metabolism
  • Humans
  • Immunologic Memory
  • In Vitro Techniques
  • Interferon-gamma / biosynthesis
  • Lymphocyte Activation
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Mucin-1 / chemistry
  • Mucin-1 / immunology
  • Necrosis
  • Peptide Fragments / chemistry
  • Peptide Fragments / immunology
  • Receptor, ErbB-2 / chemistry
  • Receptor, ErbB-2 / immunology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / transplantation*
  • T-Lymphocytes, Cytotoxic / immunology
  • Transplantation, Autologous
  • Transplantation, Heterologous


  • Antigens, Neoplasm
  • HLA-A2 Antigen
  • MUC1 tandem repeat peptide
  • Mucin-1
  • Peptide Fragments
  • Interferon-gamma
  • Receptor, ErbB-2